Citalopram hydrobromide is useful as an antidepressant. When it is used as a pharmaceutical bulk for the preparation of a pharmaceutical agent, particle size, particle size distribution and aspect ratio of the crystal are the important crystal characteristics. However, there is no teaching as to what crystal characteristics of citalopram hydrobromide are required as a beneficial pharmaceutical bulk, or a method for achieving such beneficial crystal characteristics.
According to U.S. Pat. No. 4,650,884, for example, a method for crystallizing citalopram hydrobromide comprises, crystallization in a single solvent of acetone, first recrystallization in a single solvent of water, second recrystallization in a mixed solvent of methanol and isopropyl alcohol, and third recrystallization in a mixed solvent of methanol, acetone and hexane. This method aims at purification of citalopram crystals but not at controlling particle size, particle size distribution or aspect ratio of crystals, not to mention a method for controlling these.
When citalopram hydrobromide is crystallized according to the method described in this publication, fine crystals having a particle size of less than 5 μm are formed in a large amount (41.9% of the total amount). When fine crystals are contained in a large amount, filtering performance after crystallization for medicament production is degraded. In addition, the fine particles scatter and the workers are exposed thereto during production of pharmaceutical preparations, which is an unpreferable aspect as a pharmaceutical bulk.
When citalopram hydrobromide is crystallized according to the method described in this publication, crystals having a smaller average aspect ratio of less than 2 are produced. Such crystals cause problems such as poor filtering performance after crystallization for the preparation of a pharmaceutical agent and poor fluidity when crystals are being taken out, which is not preferable as a pharmaceutical bulk.
It is therefore an object of the present invention to provide    (1) a method for industrially crystallizing citalopram hydrobromide, which method affords easy control of crystal characteristics, such as particle size, particle size distribution and aspect ratio of the crystals, and    (2) citalopram hydrobromide crystals having crystal characteristics useful as a pharmaceutical bulk.